Interleukin-2 (IL-2) is a cytokine with important regulatory properties for both T and B cells. The current studies were undertaken to evaluate IL-2 in treating HIV infection. Our studies initially focused on patients with CD4 counts above 200 cells cubic, administering IL-2 for 5 days approximately every 5 months at doses ranging from 6 to 18 million. The courses of IL-2 were well tolerated, although most patients required dose reductions because of IL-2-related adverse effects. Sustained improvement in CD4 number was seen primarily in patients with counts above 200 CD4 cells cubic. There also was a transient increase in viral load as measured by the bDNA assay seen at day 6 to 8 days after IL-2 therapy was initiated. Responses in CD4 number were less common in patients with lower baseline CD4 counts. Based on the preliminary results seen in our open trial, we undertook a randomized trial to evaluate IL-2 therapy in patients with CD4 counts above 200 cells cubic in combination with currently approved antiretroviral therapies. The study opened in April 1993 and was completed in February 1995, with 60 patients enrolling. This study also showed that intermittent therapy with IL-2 in a controlled setting can lead to a substantial and sustained increase in CD4 cell counts without leading to an increase in plasma viral load. These studies are potentially important because they are the first to suggest that immunomodulating agents combined with antiretroviral agents may benefit patients with HIV infection, primarily those with CD4 counts above 200 cells cubic.